The acid salts of sympathomimetic amines, for example, pseudoephedrine hydrochloride, are widely used active agents in over-the-counter (OTC) pharmaceuticals. As their name suggests, this class of compounds produces pharmacological effects which mimic the activation of the sympathetic nervous system. For example, the acid salt of the sympathomimetic amine, pseudoephedrine hydrochloride is a commonly used active ingredient in OTC decongestant products. It acts by causing adrenergic nerve endings to release norepinephrine, thereby stimulating alpha and beta norepinephrine receptors, particularly of the upper respiratory tract. This, in turn, results in vasoconstriction and shrinkage of swollen tissues in the sinuses and nasal passages. Its wide usage in numerous OTC products makes it readily available and easily accessible to the general public. When used in a recommended manner for approved indications, OTC pseudoephedrine hydrochloride pharmaceuticals are safe and effective. However, a problem arises when pseudoephedrine hydrochloride-containing OTC pharmaceuticals are used in an unconventional manner. Specifically, this active ingredient from OTC products is also a convenient starting material in the production of the pharmacologically active agent methamphetamine. The following references are directed to tamper resistant pseudoephedrine formulations.
U.S. Pat. No. 6,852,891 discloses a method of inhibiting or preventing the use of anhydrous ammonia as a solvent in a dissolving metal reduction process by adding to anhydrous ammonia a chemical reagent which is capable of scavenging solvated electrons generated when an alkali or alkaline earth metal is dissolved in the anhydrous ammonia containing the chemical reagent to make meth.
U.S. Pat. No. 6,359,011 and related application 2005/0256194 disclose denaturants for sympathomimetic amine salts. The denaturants include combination inhibitors, such as amino polymers, neutralized or as its salt, including salts of transition metals; reaction inhibitors such as water insoluble polyhydroxyl compounds, water soluble polyhydroxyl compounds and solvent soluble esters; and separation inhibitors such as gelling agents.
U.S. Pat. No. 6,136,864 discloses denaturants for sympathomimetic amine salts. In addition to the denaturants listed in the previous paragraph, this patent includes odor producing denaturants and encapsulated non-polar solvent soluble soap precursors and surfactants. The soap precursors include fatty acids and fatty acid esters. These products are encapsulated in a water-insoluble capsule so that they will not be released or extracted during non-polar solvent extraction, but will release in water extraction. They are viewed as being able to physically interfere with the pseudoephedrine extraction and purification, because of their effectiveness as a surfactant.
U.S. Pat. No. 6,197,314 discloses tablets containing gelling agents, with or without fats, and surfactants to impede the extraction of pseudoephedrine. In every solid dosage form using fats, the amount of fat is from about one half to one third the amount of the drug active, and much less than the claimed 20 to 50 wt. % of the present delivery system.
Tamper-resistant delivery systems using gelling agents in a drug delivery form are known in the art. When the dosage is dissolved in a small amount of water, instead of a solution, a viscous gel that cannot be injected may be formed. For combination drug systems, the gel prevents the acetaminophen from being removed by cold water extraction, because the gel retains the drugs together when extraction is attempted. U.S. Pat. Nos. 3,980,766 and 4,070,494 and U.S. patent application publications 2003/0068471, 2003/0068375, and 2007/0014732 disclose the use of gelling agents to create tamper-resistant drug delivery forms. However, often, if the amount of gelling agent is present in a sufficient amount to prevent extraction, it slows or defeats release upon ingestion.
The present application discloses that gelling agents can hinder the release of the sympathomimetic amine upon ingestion, thereby defeating the usefulness of the medication. However, the combination of an effective amount of gelling agent with a lipid can provide both the desired rapid gelling in the presence of an aqueous solvent and the desired release of the drug in the digestive system.
More importantly, the present application is directed to an orally ingested delivery system for sympathomimetic amines, particularly the acid salt of pseudoephedrine, which hinders the conversion of the pseudoephedrine acid salt to methamphetamine.